The invention relates to a mouse hybridoma clone producing a monoclonal antibody (anti-My-C-cC0C2-259-1A4; IgG1, kappa), which is directed against the cardiac myosin-binding protein C (C-protein, MYBPC3, cMyBP-C or My-C) and detects the same, and which does not react with the closely related isomers of My-C from the skeletal muscles. This monoclonal antibody is suitable as a catcher antibody or as a detection antibody for creating an enzyme-linked immunosorbent assay (ELISA) for quantitatively determining My-C in serum, plasma, whole blood or other body fluids for the early diagnosis of cardiac infarctions. Within the scope of this diagnostic procedure, this can allow a considerably early treatment of myocardial infarctions.
Due to the acute life-threatening hazard, myocardial infarctions must be diagnosed quickly and distinguished from other causes of chest pain. [1]
Determining biomarkers of myocardial necroses has meanwhile become an essential component in the diagnosis of infarctions with suspected non-ST-elevation acute coronary syndromes (NSTE-ACSs) and is imperative for making a diagnosis in the corresponding clinical context. At present, cardiac troponins (cTn) are considered the crucial biomarker. They are an integral component of the general infarction definition. [2] Cardiac troponins (cTn), however, have disadvantages, and new biomarkers could prove to be very valuable. [3]
The cTn concentration in the serum reaches a maximum only 16 to 18 hours after the onset of symptoms, and one disadvantage of the existing cTn tests is the lack of analytical sensitivity for detecting low cTn concentrations in the first hours after symptoms begin to manifest. [4; 5]
More recent cTn tests strive for a reliable determination of low cTn values; however, the reduced specificity thereof with respect to infarctions lowers the value thereof, since cTn concentrations in the vicinity of the 99th percentile of healthy test subjects can be observed.
However, even then the cTn concentrations are below this threshold in as many as 25% of the infarction patients. [6]
In view of the limited sensitivity and specificity of the cTn tests, corresponding guidelines (NICE) recommend determining the cTn 10 to 12 hours after the onset of symptoms (pain in the thoracic region) so as to confirm the diagnosis. [1]
While a number of biomarkers exist that are released more quickly after an infarction, none of these have prevailed, since these are not expressed in a cardioselective manner. [7] For this reason, current efforts are focused on analyzing the extent of the changes in the cTn concentrations over time so as to improve the validity of the cTn tests. It remains unclear how large the absolute difference in concentration would have to be to render differences in the analytical and biological variations of the cTn concentrations irrelevant for making the intended diagnosis.
The ideal biomarker would have to be released quickly from the myocardium after an infarction, but, contrary to comparable existing markers, would have to be a cardiac marker. The cardiac myosin-binding protein C (C-protein, MYBPC3, cMyBP-C or My-C) is a protein that meets these criteria. It was identified in the course of the proteomic analysis of coronary effluent from ischemic mouse hearts. [8] It is one of the most highly expressed proteins in the myocardium (19th out of 2,300 proteins), and the concentration is at least double that of cTnI and cTnT (92nd and 118th, respectively, out of 2,300 proteins). [9]
Three different My-C isomers exist, which are encoded by different genes. In contrast with the My-C of the fast skeletal muscles and the My-C of the slow skeletal muscles, the cardiac isoform has a unique N-terminal domain (FIG. 1) and other cardiac regions that could serve as specific epitopes. [10]
The release of My-C after myocardial infarctions or damage has been demonstrated [8; 11; 12; 13; 14] and the progression of the increases in the concentration over time was compared to that of cTn.